title: Prenatal exposure to bisphenol A interferes with the development of cerebellar granule neurons in mice and chicken.
abstract: In mice, prenatal exposure to low doses of bisphenol A has been shown to affect neurogenesis and neuronal migration in cortex, resulting in disturbance of both neuronal positioning and the network formation between thalamus and cortex in the offspring brain. In the present study we investigated whether prenatal exposure to bisphenol A disturbs the neurodevelopment of the cerebellum. Two different model systems were used; offspring from two strains of mice from mothers receiving bisphenol A in the drinking water before mating, during gestation and lactation, and chicken embryos exposed to bisphenol A (in the egg) on embryonic day 16 for 24h before preparation of cerebellar granule cell cultures. In the cerebellum, tight regulation of the level of transcription factor Pax6 is critical for correct development of granule neurons. During the development, the Pax6 level in granule neurons is high when these cells are located in the external granule layer and during their migration to the internal granule layer, and it is then reduced. We report that bisphenol A induced an increase in the thickness of the external granule layer and also an increase in the total cerebellar Pax6 level in 11 days old mice offspring. In cultured chicken cerebellar granule neurons from bisphenol A injected eggs the Pax6 level was increased day 6 in vitro. Together, these findings indicate that bisphenol A may affect the granule neurons in the developing cerebellum and thereby may disturb the correct development of the cerebellum.
authors.affiliation: Department of Pharmaceutical Biosciences, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, Norway. Electronic address: g.h.mathisen@farmasi.uio.no.
authors.forename: Gro H
authors.initials: GH
authors.lastname: Mathisen
authors.forename: Mazyar
authors.initials: M
authors.lastname: Yazdani
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Rakkestad
authors.forename: Petra K
authors.initials: PK
authors.lastname: Aden
authors.forename: Johanna
authors.initials: J
authors.lastname: Bodin
authors.forename: Mari
authors.initials: M
authors.lastname: Samuelsen
authors.forename: Unni C
authors.initials: UC
authors.lastname: Nygaard
authors.forename: Ingeborg L
authors.initials: IL
authors.lastname: Goverud
authors.forename: Mona
authors.initials: M
authors.lastname: Gaarder
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Anette K
authors.initials: AK
authors.lastname: Bølling
authors.forename: Rune
authors.initials: R
authors.lastname: Becher
authors.forename: Ragnhild E
authors.initials: RE
authors.lastname: Paulsen
mesh_terms: D000367:Age Factors; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D002642:Chick Embryo; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002492:Central Nervous System Depressants; D004968:Estrogens, Non-Steroidal; D000431:Ethanol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; Bisphenol A; Cerebellar granule neuron; DIV; ED; EGL; H&E; IGL; Pax6; bisphenol A; days in vitro; embryonic day; external granule layer; hematoxylin and eosin; internal granule layer